In Chemistry the recording of thermal events is a well known and established technique and calorimetric measurements for the detection of the heat of chemical or biochemical reactions have become a technique of increasing importance. It opens a very broad range of applications both for analytical purposes in fields, such as, for example, clinical, environmental and bioprocess monitoring, and for the biological study of living cells and organisms. Traditional calorimeters, which are used for such calorimetric measurements, were developed some 30 years ago. They rely on very well isolated vessels and accurate temperature regulation thanks to voluminous thermostatted baths and heat exchanger coils. Since that time, there has been a progressive appearance of new, less tedious and time consuming calorimetric measuring methods, which are based on smaller, sometimes miniaturized devices dedicated for flow-through systems and allowing a continuous and automated monitoring of various processes. Regarding the thermal detection of chemical and biochemical processes two principal approaches can be distinguished, which strongly affect the instrumentation involved.
The first approach uses calorimeters, which are based on the quasi-adiabaticity of the thermal process. In these calorimeters heat exchanges between the vessel, usually a Dewar vessel, where the reaction takes place, and the external environment must be minimized. From this demand there results the need for vessels with a large internal volume of 10 cm.sup.3 and more, for an excellent thermal insulation, for a differential arrangement and/or for an accurate compensation of the heat losses with these calorimeters. Such, an estimated amount of about 50% to 80% of the heat, which is produced in the examined chemical or biochemical process, contributes to the detected and recorded temperature change .DELTA.T.
From the prior art there are known so-called "enthalpimetric flow reactors", which work according to this first principle approach, and which are based on immobilized enzymes or microorganisms. In these devices the reaction vessel is replaced by a reactor column, that is packed with matrix-bound enzyme on a carrier substrate, where the chemical or biochemical reaction takes place. Although offering excellent performances, such as, for example, a temperature resolution of about 10.sup.-5 K, these devices suffer from several disadvantages. As the devices are based on adiabaticity they need a sophisticated insulation, which makes the whole system complicated and voluminous. Thus the dimensions of such a device are about 50 cm.times.10 cm and its weight amounts to about 2 kg. In order to be able to perform the calorimetric measurements the device used must comprise at least two thermistors (temperature dependent resistors), which have to be very well matched. However, in practice, their common mode rejection ratio (CMRR), which is a measure for the accuracy of their matching, is limited to about 1000. That means that an apparent (false) .DELTA.T of 0.001K will be observed if both thermistors are heated by 1K. Furthermore, the thermistors are part of a Wheatstone-Bridge circuitry and the necessary voltage applied to them may generate their self-heating, thus leading to artifacts. Lastly the devices suffer from the defficiencies of most devices employing columns, as these imply most of the time rather large dead volumes and hence, an increased analysis time. They are also liable to clog, especially when crude solutions from cultivation broths, or waste water samples, or samples with large molecules (e.g. cholesterol) rate to be analyzed.
The other approach is based on the principle of heat conduction. The heat, which is released during the chemical or biochemical process, is transfered from the reaction vessel to a surrounding heat sink. The heat flow between the reaction vessel and the heat sink is usually measured with a thermopile. A thermopile is a thermoelectric detector which works according to the principle of the Seebeck effect. The temperature difference across the thermocouples of the thermopile is proportionally related to a voltage between its cold and hot junctions. The sensitivities of thermopiles are typically expressed in V/W. Thus, the voltage output signal of the thermopile is proportional to the detected temperature change .DELTA.T. Such calorimeters, which are based on heat conduction, play an important role in investigations of living systems. Among these known calorimeters, which have special designs for a number of biological experiments, there are flow-through systems using flow cells, which allow the detection of released heat amounts down to some tenths of .mu.W. However, these systems also need a complicated temperature control in form of a high mass of insulating material in order to achieve the required high temperature stability and inertia. Therefore these flow cells for calorimetric measurements are voluminous, costly and exhibit long equilibration times.